BACE1 inhibitory effects of lavandulyl flavanones from Sophora flavescens

Eun Mi Hwang; Young Bae Ryu; Hoi Young Kim; Dong Gyu Kim; Seong Geun Hong; Jin Hwan Lee; Marcus J. Curtis-Long; Seong Hun Jeong; Jae Yong Park; Ki Hun Park

doi:10.1016/j.bmc.2008.05.080

BACE1 inhibitory effects of lavandulyl flavanones from Sophora flavescens

Eun Mi Hwang, Young Bae Ryu, Hoi Young Kim, Dong Gyu Kim, Seong Geun Hong, Jin Hwan Lee, Marcus J. Curtis-Long, Seong Hun Jeong, Jae Yong Park, Ki Hun Park

Research output: Contribution to journal › Article › peer-review

53 Citations (Scopus)

Abstract

In order to access β-secretase (BACE1), and enzyme strongly implicated in the cause of Alzheimer's disease, inhibitors must possess sufficient lipophilicity to traverse two lipid bilayers. Current drug candidates, which are almost totally peptide-derived, are thus inefficient because cell permeability presents a serious limiting factor. In this study, lipophilic alkylated (C₁₀-C₅) flavanones from Sophora flavescens were examined for their inhibitory effects against β-secretase. Lavandulyl flavanones (1, 2, 5, 6, and 8) showed potent β-secretase inhibitory activities with IC₅₀s of 5.2, 3.3, 8.4, 2.6, and 6.7 μM, respectively, while no significant activity was observed in the corresponding hydrated lavandulyl flavanones (4 and 7) and prenylated flavanone (3). As we expected, lavandulyl flavanones reduced Aβ secretion dose-dependently in transfected human embryonic kidney (HEK-293) cells. In kinetic studies, all compounds screened were shown to be noncompetitive inhibitor.

Original language	English
Pages (from-to)	6669-6674
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry
Volume	16
Issue number	14
DOIs	https://doi.org/10.1016/j.bmc.2008.05.080
Publication status	Published - 2008 Jul 15
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by grants from the Korea Science and Engineering Foundation (R13-2005-012-02002-0) and the MOST/KOSEF to the Environmental Biotechnology National Core Research Center (R15-2003-012-02001-0). Y.B. Ryu was supported by a scholarship from the BK21 program, the Ministry of Education and Human Resources Development, Korea.

Keywords

Alzheimer's disease
BACE1
HEK 293
Lavandulyl flavanone
Sophora flavescens

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bmc.2008.05.080

Cite this

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title = "BACE1 inhibitory effects of lavandulyl flavanones from Sophora flavescens",

abstract = "In order to access β-secretase (BACE1), and enzyme strongly implicated in the cause of Alzheimer's disease, inhibitors must possess sufficient lipophilicity to traverse two lipid bilayers. Current drug candidates, which are almost totally peptide-derived, are thus inefficient because cell permeability presents a serious limiting factor. In this study, lipophilic alkylated (C10-C5) flavanones from Sophora flavescens were examined for their inhibitory effects against β-secretase. Lavandulyl flavanones (1, 2, 5, 6, and 8) showed potent β-secretase inhibitory activities with IC50s of 5.2, 3.3, 8.4, 2.6, and 6.7 μM, respectively, while no significant activity was observed in the corresponding hydrated lavandulyl flavanones (4 and 7) and prenylated flavanone (3). As we expected, lavandulyl flavanones reduced Aβ secretion dose-dependently in transfected human embryonic kidney (HEK-293) cells. In kinetic studies, all compounds screened were shown to be noncompetitive inhibitor.",

keywords = "Alzheimer's disease, BACE1, HEK 293, Lavandulyl flavanone, Sophora flavescens",

author = "Hwang, {Eun Mi} and Ryu, {Young Bae} and Kim, {Hoi Young} and Kim, {Dong Gyu} and Hong, {Seong Geun} and Lee, {Jin Hwan} and Curtis-Long, {Marcus J.} and Jeong, {Seong Hun} and Park, {Jae Yong} and Park, {Ki Hun}",

note = "Funding Information: This work was supported by grants from the Korea Science and Engineering Foundation (R13-2005-012-02002-0) and the MOST/KOSEF to the Environmental Biotechnology National Core Research Center (R15-2003-012-02001-0). Y.B. Ryu was supported by a scholarship from the BK21 program, the Ministry of Education and Human Resources Development, Korea. ",

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AU - Kim, Dong Gyu

AU - Hong, Seong Geun

AU - Lee, Jin Hwan

AU - Curtis-Long, Marcus J.

AU - Jeong, Seong Hun

AU - Park, Jae Yong

AU - Park, Ki Hun

N1 - Funding Information: This work was supported by grants from the Korea Science and Engineering Foundation (R13-2005-012-02002-0) and the MOST/KOSEF to the Environmental Biotechnology National Core Research Center (R15-2003-012-02001-0). Y.B. Ryu was supported by a scholarship from the BK21 program, the Ministry of Education and Human Resources Development, Korea.

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N2 - In order to access β-secretase (BACE1), and enzyme strongly implicated in the cause of Alzheimer's disease, inhibitors must possess sufficient lipophilicity to traverse two lipid bilayers. Current drug candidates, which are almost totally peptide-derived, are thus inefficient because cell permeability presents a serious limiting factor. In this study, lipophilic alkylated (C10-C5) flavanones from Sophora flavescens were examined for their inhibitory effects against β-secretase. Lavandulyl flavanones (1, 2, 5, 6, and 8) showed potent β-secretase inhibitory activities with IC50s of 5.2, 3.3, 8.4, 2.6, and 6.7 μM, respectively, while no significant activity was observed in the corresponding hydrated lavandulyl flavanones (4 and 7) and prenylated flavanone (3). As we expected, lavandulyl flavanones reduced Aβ secretion dose-dependently in transfected human embryonic kidney (HEK-293) cells. In kinetic studies, all compounds screened were shown to be noncompetitive inhibitor.

AB - In order to access β-secretase (BACE1), and enzyme strongly implicated in the cause of Alzheimer's disease, inhibitors must possess sufficient lipophilicity to traverse two lipid bilayers. Current drug candidates, which are almost totally peptide-derived, are thus inefficient because cell permeability presents a serious limiting factor. In this study, lipophilic alkylated (C10-C5) flavanones from Sophora flavescens were examined for their inhibitory effects against β-secretase. Lavandulyl flavanones (1, 2, 5, 6, and 8) showed potent β-secretase inhibitory activities with IC50s of 5.2, 3.3, 8.4, 2.6, and 6.7 μM, respectively, while no significant activity was observed in the corresponding hydrated lavandulyl flavanones (4 and 7) and prenylated flavanone (3). As we expected, lavandulyl flavanones reduced Aβ secretion dose-dependently in transfected human embryonic kidney (HEK-293) cells. In kinetic studies, all compounds screened were shown to be noncompetitive inhibitor.

KW - Alzheimer's disease

KW - BACE1

KW - HEK 293

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BACE1 inhibitory effects of lavandulyl flavanones from Sophora flavescens

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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